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Atherosclerosis surrogate imaging trials come of age: For better or for worse?

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Abstract

Surrogate atherosclerosis imaging trials have been used to evaluate drugs for regulatory approval. These imaging trials have focused on two methodologies: carotid B-mode ultrasound to measure carotid intima-media thickness (CIMT) and coronary intravascular ultrasound (IVUS) to assess atheroma volume. Recent controversies exist regarding the clinical use of these imaging trials. However, a review of the published CIMT and IVUS trials demonstrates consistent results if the trial is conducted in a coordinated fashion. Proper patient selection appears to be an important criterion to ascertain valid results, especially for CIMT trials. In light of the cost and time involved to complete morbidity trials demonstrating the benefit of potential antiatherosclerotic agents, surrogate imaging trials are necessary to expedite the regulatory approval process.

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References and Recommended Reading

  1. DiMasi JA, Hansen RW, Grabowski HG: The price of innovation: new estimates of drug development costs. J Health Econ 2003, 22:151–185.

    Article  PubMed  Google Scholar 

  2. Smilde TJ, van Wissen S, Wollersheim H, et al.: Effect of aggressive versus conventional lipid lowering on atherosclerosis progression in familial hypercholesterolaemia (ASAP): a prospective, randomised, double-blind trial. Lancet 2001, 357:577–581.

    Article  PubMed  CAS  Google Scholar 

  3. Nissen SE, Tuzcu EM, Schoenhagen P, et al.: Effect of intensive compared with moderate lipid-lowering therapy on progression of coronary atherosclerosis: a randomized controlled trial. JAMA 2004, 291:1071–1080.

    Article  PubMed  CAS  Google Scholar 

  4. Ridker PM, Morrow DA, Rose LM, et al.: Relative efficacy of atorvastatin 80 mg and pravastatin 40 mg in achieving the dual goals of low-density lipoprotein cholesterol <70 mg/dl and C-reactive protein <2 mg/l: an analysis of the PROVE-IT TIMI-22 trial. J Am Coll Cardiol 2005, 45:1644–1648.

    Article  PubMed  CAS  Google Scholar 

  5. LaRosa JC, Grundy SM, Waters DD, et al.: Intensive lipid lowering with atorvastatin in patients with stable coronary disease. N Engl J Med 2005, 352:1425–1435.

    Article  PubMed  CAS  Google Scholar 

  6. Pedersen TR, Faergeman O, Kastelein JJ, et al.: High-dose atorvastatin vs usual-dose simvastatin for secondary prevention after myocardial infarction: the IDEAL study: a randomized controlled trial. JAMA 2005, 294:2437–2445.

    Article  PubMed  CAS  Google Scholar 

  7. Nissen SE, Tuzcu EM, Brewer HB, et al.: Effect of ACAT inhibition on the progression of coronary atherosclerosis. N Engl J Med 2006, 354:1253–1263.

    Article  PubMed  CAS  Google Scholar 

  8. Meuwese MC, Duivenvoorden R, Davidson MH, et al.: Effect of ACAT inhibition on progression of carotid atherosclerosis in patients with familial hypercholesterolemia. The CAPTIVATE study. Poster presented at the Drugs Affecting Lipid Metabolism meeting. New York, NY; October 4–7, 2007.

  9. Nissen SE, Tardif JC, Nicholls SJ, et al.: Effect of torcetrapib on the progression of coronary atherosclerosis. N Engl J Med 2007, 356:1304–1316.

    Article  PubMed  CAS  Google Scholar 

  10. Kastelein JJ, van Leuven SI, Burgess L, et al.: Effect of torcetrapib on carotid atherosclerosis in familial hypercholesterolemia. N Engl J Med 2007, 356:1620–1630.

    Article  PubMed  CAS  Google Scholar 

  11. Bots ML, Visseren FL, Evans GW, et al.: Torcetrapib and carotid intima-media thickness in mixed dyslipidaemia (RADIANCE 2 study): a randomised, double-blind trial. Lancet 2007, 370:153–160.

    Article  PubMed  CAS  Google Scholar 

  12. Mazzone T, Meyer PM, Feinstein SB, et al.: Effect of pioglitazone compared with glimepiride on carotid intima-media thickness in type 2 diabetes: a randomized trial. JAMA 2006, 296:2572–2581.

    Article  PubMed  CAS  Google Scholar 

  13. Nissen SE, Nicholls SJ, Wolski K, et al.: Comparison of pioglitazone vs glimepiride on progression of coronary atherosclerosis in patients with type 2 diabetes: the PERISCOPE randomized controlled trial. JAMA 2008, 299:1561–1573.

    Article  PubMed  CAS  Google Scholar 

  14. Crouse JR 3rd, Raichlen JS, Riley WA, et al.: Effect of rosuvastatin on progression of carotid intima-media thickness in low-risk individuals with subclinical atherosclerosis: the METEOR trial. JAMA 2007, 297:1344–1353.

    Article  PubMed  CAS  Google Scholar 

  15. Nissen SE, Nicholls SJ, Wolski K, et al.: Effect of rimonabant on progression of atherosclerosis in patients with abdominal obesity and coronary artery disease: the STRADIVARIUS randomized controlled trial. JAMA 2008, 299:1547–1560.

    Article  PubMed  CAS  Google Scholar 

  16. Kastelein JJ, Akdim F, Stroes ES, et al.: Simvastatin with or without ezetimibe in familial hypercholesterolemia. N Engl J Med 2008, 358:1431–1443.

    Article  PubMed  CAS  Google Scholar 

  17. Barter PJ, Caulfield M, Eriksson M, et al.: Effects of torcetrapib in patients at high risk for coronary events. N Engl J Med 2007, 357:2109–2122.

    Article  PubMed  CAS  Google Scholar 

  18. Dormandy JA, Charbonnel B, Eckland DJ, et al.: Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events): a randomised controlled trial. Lancet 2005, 366:1279–1289.

    Article  PubMed  CAS  Google Scholar 

  19. Nissen SE, Nicholls SJ, Sipahi I, et al.: Effect of very high-intensity statin therapy on regression of coronary atherosclerosis: the ASTEROID trial. JAMA 2006, 295:1556–1565.

    Article  PubMed  CAS  Google Scholar 

  20. Simon T, Boutouyrie P, Gompel A, et al.: Rationale, design and methods of the CASHMERE study. Fundam Clin Pharmacol 2004, 18:131–138.

    Article  PubMed  CAS  Google Scholar 

  21. Deedwania P, Barter P, Carmena R, et al.: Reduction of low-density lipoprotein cholesterol in patients with coronary heart disease and metabolic syndrome: analysis of the Treating to New Targets study. Lancet 2006, 368:919–928.

    Article  PubMed  CAS  Google Scholar 

  22. Nicholls SJ, Tuzcu EM, Kalidindi S, et al.: Effect of diabetes on progression of coronary atherosclerosis and arterial remodeling: a pooled analysis of 5 intravascular ultrasound trials. J Am Coll Cardiol 2008, 52:255–262.

    Article  PubMed  CAS  Google Scholar 

  23. ClinicalTrials.gov: Atherosclerosis Underlying Development Assessed by Intima-Media Thickness in Patients on Rimonabant (Auditor). Available at http://clinicaltrials.gov/ct2/show/NCT00228176?term=AUDITOR»nk=1. Accessed August 26, 2008.

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Correspondence to Michael H. Davidson.

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Davidson, M.H., Dembowski, E. Atherosclerosis surrogate imaging trials come of age: For better or for worse?. Curr Cardiol Rep 10, 521–525 (2008). https://doi.org/10.1007/s11886-008-0081-6

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  • DOI: https://doi.org/10.1007/s11886-008-0081-6

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